While it is contemplated that the method and apparatus of the present invention may be used for prilling of substances other than pharmaceutical mixtures, the present invention arose from a need for packaging of pharmaceuticals in small particles. Thus, by way of example, the present invention will be described in connection with production of pharmaceutical prills.
Many drugs are known to upset the stomach or be inactivated by acidic gastric contents. To be given orally, such drugs must be enteric coated. Due, for example to the randomness of stomach emptying, provision of such a coated drug as a large number of individual coated particles improves the uniformity of drug release than would provision of the same dosage in a single tablet or capsule.
The present applicant is aware of multi-particulate dosage forms, such as micropellets, medules, spansules and others. Both are generally satisfactory but have drawbacks. Micropellets have a cylindrical shape which is difficult to coat. Medules, spansules, etc. have not been found suitable for high drug dosages. All forms are relatively expensive to produce.
A process known as prilling has been used in various industries to produce small particles. Classically, prilling consists of melting a material, allowing it to fall in a narrow stream through an orifice, permitting the stream to break up as it falls into discrete droplets and then permitting the droplets to congeal as they fall further.
For example, urea prills have been produced for fertilizer in large amounts at low cost in commercial prilling towers.
These towers are generally in excess of 300 feet high to permit sufficient cooling time to congeal the prills.
However, such a prilling arrangement was unsatisfactory for the pharmaceutical task at hand, for example in view of the great height of such a conventional prilling tower, which substantially exceeds the height limitations in conventional pharmaceutical plant buildings and would be costly to construct. Further, this prior prilling process disadvantageously would require substantial tower diameter in view of the tendency of the forming prills to spread laterally as they fall. Moreover, such prior prilling systems have yielded prills which vary substantially in diameter, resulting in the need for screening of prills and either recycling or loss of under-and oversized prills. Additionally, the use of such very large prior prilling towels to handle pharmaceuticals, in view of the potency of the raw drug, possible irritation of plant personnel which could be caused by handling of sophisticated pharmaceuticals and chemicals, and the overall safety of the process, would produce substantial problems.
An attempt was made to overcome the problems of such conventional prilling techniques by use of a modified prilling head wherein molten prill mix was forced out of a nozzle in a steady stream, such stream being intersected after leaving the nozzle by three converging streams of air which compress the prill mix stream and then break it up into a shower of droplets. While this reduced the fall height required to solidify the prills, it had major disadvantages, including a highly non-homogenous particle size range and a wide area distribution of finished particles (requiring that such particles be collected from, for example a 24-square-foot area).
Other known methods for forming small spherical pellets of the type desired were found to have one or more disadvantages rendering same unacceptable for the intended use.
During the development of the present invention it was determined that a proper vehicle for the drug must be found, it usually being nonfeasible to melt the drug directly. Requirements for the vehicle included low cost, capability to melt at reasonably low temperature, and capability to act as a good solvent for the drug such that the molten vehicle can dissolve the drug without decomposition of the latter. On the other hand, the vehicle melt temperature cannot be too low or same will not congeal into prills. Once congealed, it must be hard enough to be handled by sizing and coating equipment. Also, such vehicle must be compatible with coating materials for the resultant particles and must dissolve easily in water. Finally, it was determined that such vehicle must be safe for internal use. As hereinafter discussed, such vehicle was found.
The objects and purposes of the present invention include provision of:
1. A method and apparatus for prilling, particularly of pharmaceutical materials, allowing formation of substantially spherical particles in large quantity per unit time and at low cost.
2. A method and apparatus, as aforesaid, capable of forming uniformly sized prills within a relatively short and small diameter drop zone from which solidified prills can be readily gathered and wherein the coolant fluid in the drop zone may be a liquid or gas, such as air.
3. A method and apparatus, as aforesaid, in which prill size and rate of production are precisely controlled by a voltage wave form, wherein the pressure and temperature of the prill mix are precisely controllable, and wherein the apparatus can be constructed largely from readily available commercial parts at low cost.
4. A method and apparatus, as aforesaid, in which dropping of a stream of molten prill material is eliminated and the apparatus includes one or more reciprocable valve members which admit the molten prill material to the coolant fluid in the form of initially separated droplets.
5. A method and apparatus, as aforesaid, capable of forming enteric coatable prills suitable for use in multiparticulate dosages.
6. A method and apparatus, as aforesaid, capable of employing an inexpensive vehicle for the drug to be prilled, which vehicle is capable of melting at a relatively low temperature and is capable of acting as a good solvent for drugs of interest without effecting decomposition of such drug, which is capable of congealing under room temperature conditions and upon congealing is sufficiently hard to be handled by conventional sizing and coating equipment, which is compatible with conventional coating materials and dissolves easily in water and which is safe for internal use.
7. A method and apparatus, as aforesaid, wherein one or more hot melt glue guns are adapted to separate melted pharmaceutical prill mixture into a series of droplets of closely controlled size and frequency before dropping through a cooling fluid.
Other objects and purposes of the invention will be apparent to persons acquainted with apparatus and methods of this general type upon reading the following specification and inspecting the accompanying drawings.